Mitotic exit regulation through distinct domains within the protein kinase Cdc15

Mol Cell Biol. 2003 Jul;23(14):5018-30. doi: 10.1128/MCB.23.14.5018-5030.2003.

Abstract

The mitotic exit network (MEN), a Ras-like signaling cascade, promotes the release of the protein phosphatase Cdc14 from the nucleolus and is essential for cells to exit from mitosis in Saccharomyces cerevisiae. We have characterized the functional domains of one of the MEN components, the protein kinase Cdc15, and investigated the role of these domains in mitotic exit. We show that a region adjacent to Cdc15's kinase domain is required for self-association and for binding to spindle pole bodies and that this domain is essential for CDC15 function. Furthermore, we find that overexpression of CDC15 lacking the C-terminal 224 amino acids results in hyperactivation of MEN and premature release of Cdc14 from the nucleolus, suggesting that this domain within Cdc15 functions to inhibit MEN signaling. Our findings indicate that multiple modes of MEN regulation occur through the protein kinase Cdc15.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Green Fluorescent Proteins
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mitosis*
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases
  • Protein Structure, Tertiary / physiology
  • Protein Transport / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Telophase / genetics

Substances

  • CDC15 protein
  • Cell Cycle Proteins
  • Luminescent Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • TEM1 protein, S cerevisiae
  • Green Fluorescent Proteins
  • Protein Kinases
  • DBF2 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • GTP-Binding Proteins
  • Monomeric GTP-Binding Proteins